Cerenkov luminescence endoscopy: improved molecular sensitivity with β--emitting radiotracers

Abstract

Cerenkov luminescence endoscopy (CLE) is an optical technique that captures the Cerenkov photons emitted from highly energetic moving charged particles (β(+) or β(-)) and can be used to monitor the distribution of many clinically available radioactive probes. A main limitation of CLE is its limited sensitivity to small concentrations of radiotracer, especially when used with a light guide. We investigated the improvement in the sensitivity of CLE brought about by using a β(-) radiotracer that improved Cerenkov signal due to both higher β-particle energy and lower γ noise in the imaging optics because of the lack of positron annihilation.

Methods: The signal-to-noise ratio (SNR) of (90)Y was compared with that of (18)F in both phantoms and small-animal tumor models. Sensitivity and noise characteristics were demonstrated using vials of activity both at the surface and beneath 1 cm of tissue. Rodent U87MG glioma xenograft models were imaged with radiotracers bound to arginine-glycine-aspartate (RGD) peptides to determine the SNR.

Results: γ noise from (18)F was demonstrated by both an observed blurring across the field of view and a more pronounced fall-off with distance. A decreased γ background and increased energy of the β particles resulted in a 207-fold improvement in the sensitivity of (90)Y compared with (18)F in phantoms. (90)Y-bound RGD peptide produced a higher tumor-to-background SNR than (18)F in a mouse model.

Conclusion: The use of (90)Y for Cerenkov endoscopic imaging enabled superior results compared with an (18)F radiotracer.

Keywords: Cerenkov luminescence endoscopy; Cerenkov luminescence imaging; radionuclides; β-emitter.

FIGURE 1

(A) Sensitivity comparison between ¹⁸F and ⁹⁰Y. (B) Comparison between tracer SNR normalized for activity and light output, which is dependent on charged-particle energy.

FIGURE 2

(A and B) CLE emission (A) and CLE overlay (B) over ambient-light image of ¹⁸F vial covered with 1 cm of chicken breast. (C and D) CLE emission (C) and CLE overlay (D) over ambient-light image of ⁹⁰Y vial covered with 1 cm of chicken breast. (E) Cross-sectional plot of line response of signal across 1 row of imaging fiber bundle, with 0 defined as optical axis. (F) Background noise (region outside vial containing radiotracer) in imaging fiber bundle vs. distance from vial to endoscope (in inches). a.u. = arbitrary units.

FIGURE 3

In vivo comparison of CLE improvement using ⁹⁰Y-PRGD₂ vs. ¹⁸F-FP-PRGD₂. (A and B) Biodistribution results comparing tumor and muscle (A) and tumor-to-muscle (T/M) ratio (B) for both peptides. (C) Tumor-to-background ratio from ⁹⁰Y-PRGD₂ vs. ¹⁸F-FP-PRGD₂ for all 4 mice as determined by CLE. (D and E) CLE image (D) and ambient-light overlay (E) of ⁹⁰Y-PRGD₂ emitted from mouse flank. (F and G) CLE image (F) and ambient-light overlay (G) of ¹⁸F-FP-PRGD₂ emitted from mouse flank.